Sulfuric Acid → (S)-5-acetyl-N-(1-(3-(4-cyano-3-iodophenyl)-1H-pyrazol-1-yl)propan-2-yl)-1H-pyrazole-3-carboxamide

HRID 872592Notes

Reaction equation

HRID 872592 reaction equation
N([O-])=O.[Na+].[C:5]([C:8]1[CH:12]=[C:11]([C:13]([NH:15][C@@H:16]([CH3:34])[CH2:17][N:18]2[CH:22]=[CH:21][C:20]([C:23]3[CH:28]=[CH:27][C:26]([C:29]#[N:30])=[C:25]([N+]([O-])=O)[CH:24]=3)=[N:19]2)=[O:14])[NH:10][N:9]=1)(=[O:7])[CH3:6].S(=O)(=O)(O)O.[I-:40].[K+]>O.CC#N>[C:5]([C:8]1[NH:9][N:10]=[C:11]([C:13]([NH:15][C@@H:16]([CH3:34])[CH2:17][N:18]2[CH:22]=[CH:21][C:20]([C:23]3[CH:28]=[CH:27][C:26]([C:29]#[N:30])=[C:25]([I:40])[CH:24]=3)=[N:19]2)=[O:14])[CH:12]=1)(=[O:7])[CH3:6]

Participants

7

Reactant 4

HCID 1118Sulfuric AcidHCID 4875Potassium IodideHCID 23668193Sodium NitriteHCID 67172191(S)-3-acetyl-N-(1-(3-(4-cyano-3-nitrophenyl)-1H-pyrazol-1-yl)propan-2-yl)-1H-pyrazole-5-carboxamide

Product 1

HCID 178466825(S)-5-acetyl-N-(1-(3-(4-cyano-3-iodophenyl)-1H-pyrazol-1-yl)propan-2-yl)-1H-pyrazole-3-carboxamideYield 23.3%

Reagents, catalysts & solvents 2

HCID 962WaterSolvent4×HCID 6342AcetonitrileSolvent

Procedure

Sodium nitrite (50 mg, 0.73 mmol) in 1 ml of water was added slowly to a solution of (S)-3-acetyl-N-(1-(3-(4-cyano-3-nitrophenyl)-1H-pyrazol-1-yl)propan-2-yl)-1H-pyrazole-5-carboxamide (250 mg, 0.66 mmol) in water (2 ml), sulfuric acid (71 μl, 1.33 mmol) and MeCN (3 ml) at 0° C. After 15 min potassium iodide (0.22 g, 1.32 mmol) in 1 ml of water was added. Reaction mixture was stirred at RT for 2 h and then poured into 10 ml of water. Thus resulting precipitate was filtered and washed with 10% sodium bisulfite solution and water. Crude product was purified by CombiFlash (column: silica, eluent: 3-10% MeOH in DCM) to yield 75 mg (23%) of the title compound. 1H-NMR (400 MHz; MeOD): δ 1.27 (d, 3H), 2.55 (s, 3H), 4.35 (m, 1H), 4.39 (m, 1H), 4.57 (m, 1H), 6.63 (d, 1H), 7.28 (br s, 1H), 7.42 (s, 1H), 7.57 (d, 1H), 7.66 (d, 1H), 7.93 (br s, 1H), 8.35 (s, 1H).

Workup

  1. customReaction mixture
  2. customThus resulting precipitate
  3. filtrationwas filtered
  4. washwashed with 10% sodium bisulfite solution and water
  5. customCrude product was purified by CombiFlash (column: silica, eluent: 3-10% MeOH in DCM)

Sources & evidence

ORD record
ord-ec882ce1156246b5a921c5f0c32422d3
Source dataset
uspto-grants-2015_03
Patent number
US08975254B2

Reaction notes

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